STAT1, NF-κB and ERKs play a role in the induction of lipocalin-2 expression in adipocytes ★

Lipocalin-2 (LCN2) is induced in conditions of obesity and Type 2 diabetes (T2DM). IFNγ and TNFα induce LCN2 expression in adipocytes in a manner that is dependent on transcription. The effects of these cytokines are additive. IFNγ induced STAT1 and TNFα induced NF-κB play a role in the induction of LCN2. In the LCN2 promoter, one NF-κB binding site and four STAT1 binding sites were identified by in silico and in vitro approaches. MAPK (ERKs 1 and 2) activation was required for the IFNγ and TNFα induction of LCN2 expression, but did not affect the nuclear translocation or DNA binding activity of STAT1 or NF-κB. The NF-κB binding site and the STAT1 binding sites we identified in vitro were confirmed by in vivo studies. Transfection of a LCN2 promoter/luciferase reporter construct confirmed acute activation by IFNγ and TNFα. Our studies identify mechanisms involved in the actions of cytokines secreted from immune cells in adipose tissue that induce LCN2 expression in conditions of obesity and T2DM.